Abstract
BackgroundKetosis can be induced in humans and in animals by fasting or dietary interventions, such as ketogenic diets. However, the increasing interest on the ketogenic state has motivated the development of alternative approaches to rapidly increase ketonemia using less drastic interventions. Here, it was tested whether oral intake of a β-hydroxybutyrate (βHB) mineral salt mixture could increase ketonemia in Wistar rats without any other dietary changes, thereby being a useful model to study ketones effects alone on metabolism.MethodsβHB salts were orally administered to provoke elevation in the ketonemia. Effects of this intervention were tested acutely (by gavage) and chronically (4 weeks in drinking water). Acutely, a concomitant glucose overload was used to suppress endogenous ketogenesis and verify whether βHB salts were really absorbed or not. Long-term administration allowed to weekly evaluate the impact on ketonemia, blood glucose and, after 4 weeks, on body weight, visceral fat mass, lipid blood profile, serum lipolysis products and adiponectinemia.ResultsβHB salts increased ketonemia in acute and long-term administrations, improved blood lipid profile by raising HDL-cholesterol concentration and decreasing LDL/HDL ratio, while reduced visceral adipocyte volume. Mean ketonemia correlated positively with HDLc and negatively with adipocyte volume and serum lipolysis products.ConclusionsOral βHB can rapidly increase ketonemia and, therefore, be used as an acute and long-term animal model of ketosis. Long-term treatment points to important beneficial effects of ketone bodies in serum lipid concentrations and visceral fat mass. These results may help to explain the metabolic adaptations following ketogenic diets, such as a better body fat control and a serum lipid profile improvement.
Highlights
Ketosis can be induced in humans and in animals by fasting or dietary interventions, such as ketogenic diets
Oral βHB impact on ketonemia Oral administration of βHB salts increased ketonemia (Fig. 1a) compared to control during all the time tested (2 h), even during concomitant administration of glucose (Fig. 1b) intended to suppress endogenous ketogenesis, showing that elevation of blood βHB was caused by βHB exogenous supplementation
The average determination of blood ketone bodies along the 4 weeks was about 22% higher in βHB supplemented vs. control rats in Zeitgeber hours (ZT) 14–16 (Fig. 2b), while the ketonemia values obtained at ZT 0–1 were 51% more elevated in average during the 4-week period in the supplemented
Summary
Ketosis can be induced in humans and in animals by fasting or dietary interventions, such as ketogenic diets. The dietary carbohydrate restriction associated with ketogenic diets by itself and the parallel increase in protein/lipid consumption, as well as the state of nutritional ketosis, are all potential mechanisms to explain the better weight control, blood lipid profile and glycemic improvement seen in protocols which use Caminhotto et al Nutrition & Metabolism (2017) 14:31 ketogenic diets. In this sense, few works have dealed with more direct and strict effects of ketones in evoking the above clinical picture. ΒHB mineral salts supplementation has produced a significant hypoglycemic effect when in combination with MCT oil while alone decreased the body weight gain after 4 weeks of treatment, all aspects that are influenced by ketogenic diets
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